Recent Advances of Small Molecule Focal Adhesion Kinase (FAK) Inhibitors as Promising Anticancer Therapeutics

Focal Adhesion Kinase (FAK) is a non-receptor tyrosine kinase involved in the process of cell proliferation, survival, migration, and invasion. It has become a promising therapeutic target for the treatment of human metastatic cancers due to its overexpression and/or activation in multiple cancer types. Since FAK is emerging as a potential cancer target because of its overexpression at both the transcriptional and translational level in cancer, different types of FAK inhibitors with diversified scaffolds have been discovered in the past few years. In this review, the progress of recently discovered small molecule FAK inhibitors was summarized. Major efforts have been focused on the rational design and synthesis of small molecule FAK inhibitors, and their structure-activity relationship (SAR) analysis wasalso discussed. Among them, while type I inhibitors remain as the major focuses, type II inhibitors and novel allosteric FAK inhibitors (type III inhibitors) have been developed to improve both potency and selectivity. Meanwhile, novel strategies, such as targeting FAK using inhibitors of protein-protein interactions, were also discovered. Lastly, some insights and perspectives on the future development of FAK inhibitors as anticancer therapeutics have been provided.

Automated summary

FAK, a non-receptor tyrosine kinase, has emerged as a potential therapeutic target for human metastatic cancers due to its overexpression. Recent progress in small molecule FAK inhibitors includes the development of type I, II, and III inhibitors, as well as inhibitors targeting FAK using protein-protein interactions. Insights and perspectives on the future development of FAK inhibitors as anticancer therapeutics have also been provided.